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ADVL1621, MK-3475-051, A Phase I/II Study of Pembrolizumab (MK-3475) in Children with advanced melanoma or a PD-L1 positive advanced, relapsed or refractory solid tumor or lymphoma (KEYNOTE-051)
Study ID: STU 052016-090
This is a two-part Phase i-ii, nonrandomized, open-label, single-arm, multi-center trial to evaluate the pharmacokinetics (PK), pharmacodynamics, toxicity, safety, and anti-tumor activity of MK-3475 (also known as pembrolizumab) in pediatric subjects aged 6 months to less than 18 years of age with either advanced melanoma or a programmed death-ligand 1 (PD-L1) positive advanced, relapsed or refractory solid tumor or lymphoma. While this trial's primary efficacy goals are to evaluate anti-tumor activity in PD-L1 positive tumors, preliminary exploration of antitumor activity will also be conducted in a subset of PD-L1 negative tumors based upon response observed in PD-L1 positive tumors or lymphoma in this trial.
1. Be willing and able to provide written informed consent/assent for the trial. The subject may also provide consent/assent for Future Biomedical Research. However, the subject may participate in the main trial without participating in Future Biomedical Research. 2. Be between 6 months and less than 18 years of age on day of signing informed consent/assent. Note: the first three patients dosed in Part 1 are to be >= 6 years of age. 3. Have histologically or cytologically-documented, locally-advanced, or metastatic solid malignancy that is incurable and has either (a) failed prior standard therapy, (b) for which no standard therapy exists, or (c) standard therapy is not considered appropriate by the patient and treating physician. There is no limit to the number of prior treatment regimens. 4. Be able to provide tissue from an archival tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated (tumors progressing in a prior site of radiation are allowed for characterization, other exceptions may be considered after Sponsor consultation). Of note, samples that require decalcification are not allowed. 5. Have either advanced melanoma or a programmed death-ligand 1 (PD-L1) positive advanced, relapsed or refractory solid tumor or lymphoma as determined by immunohistochemistry (IHC) in archival formalin fixed paraffin embedded tumor (FFPET) or newly obtained biopsy to qualify for the PD-L1 positive cohorts in Part I and II of this trial. For this trial, tumor specimens with positive stroma or at least 1% of cells expressing PD-L1 by IHC will be defined as PD-L1 positive. Subjects with PD-L1 negative tumors may be enrolled during Part II of this trial in select tumor types (following direct communication from the Sponsor). For these subjects, PD-L1 status must be determined by IHC in archival FFPET or newly obtained biopsy. 6. Have measurable disease based on Response Evaluation Criteria In Solid Tumors (RECIST) 1.1. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions. Subjects with neuroblastoma who do not have measurable disease per RECIST 1.1 but have metaiodobenzylguanidine (MIBG)-positive evaluable disease may be enrolled. 7. Have a performance status as defined below: - Lansky Play Scale >= 50 for children up to and including 16 years of age; - Karnofsky score >= 50 for children > 16 years of age - Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score. 8. Demonstrate adequate organ function as defined below: Hematological: -For patients with solid tumors without bone marrow involvement: Absolute neutrophil count (ANC) >= 1,000 /mcL Platelets >= 100,000/mcL Hemoglobin >= 8 g/dL -For patients with solid tumors and known bone marrow metastatic disease: Absolute neutrophil count (ANC) >= 750 /mcL Platelets >= 50,000/mcL Hemoglobin >= 8 g/dL Renal: Creatinine by age/gender, as defined in the protocol OR Measured or calculated creatinine clearance >= 70 mL/min/1.73 m2 Hepatic: -Total bilirubin <= 1.5xULN (upper limit of normal) for age OR Direct bilirubin <=ULN for age for subjects with total bilirubin levels > 1.5xULN for age -Alanine aminotransferase (ALT) serum glutamic-pyruvic transaminase (SGPT) <= 110 U/L (for the purpose of this study, the ULN for SGPT is 45 U/L) -Serum albumin >= 2 g/dL 9. Female subject of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. 10. Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Subjects of childbearing potential are those who have begun menstruating and have not been surgically sterilized. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject. 11. Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject. Applicable to Part I of the study ONLY 12. Six of the 12 subjects in a given dose finding/dose confirmation cohort (i.e., Part I) must weigh >= 16 kg (a minimum of 6 subjects at any given dose are needed for the interleukin-2 (IL-2) assay, and subjects must weigh >= 16 kg in order to provide a specimen for IL-2 analysis).
- Cancer Related
- Healthy Volunteers
- UT Southwestern Principal Investigator
- Theodore W Laetsch
CHILDRENS ONCOLOGY GROUP OPERATIONS CTR
Lymphoma; Melanoma, skin; Other